This project investigates genetic deficiencies in pulmonary surfactant proteins that cause respiratory disease in newborns. The goals of this study are to diagnose inherited abnormalities of surfactant proteins in infants with respiratory distress, identify new mutations and study surfactant metabolism in tissue of affected infants, and finally, to determine effects of recombinant surfactant protein expression in deficeint tissue. During the past year we have tested for surfactant protein deficiency in both bronchoalveolar lavage fluid using western protein analysis and by PCR analysis of DNA to detect known mutations. We have identified two infants with surfactant protein abnormalities apprently due to a previously unidentified mutation. Analysis of the surfactant protein B gene for these two infants is underway. In addition, we have carried out studies of surfactant metabolism in five specimens of lung received either at transplantation or postmortem.